The Experts below are selected from a list of 156 Experts worldwide ranked by ideXlab platform
Blanca I Aldana - One of the best experts on this subject based on the ideXlab platform.
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distinct differences in rates of Oxygen Consumption and atp synthesis of regionally isolated non synaptic mouse Brain mitochondria
Journal of Neuroscience Research, 2019Co-Authors: Jens V Andersen, Emil Jakobsen, Helle S Waagepetersen, Blanca I AldanaAbstract:Brain mitochondrial dysfunction has been implicated in several neurodegenerative diseases. The distribution and efficiency of mitochondria display large heterogeneity throughout the regions of the Brain. This may imply that the selective regional susceptibility of neurodegenerative diseases could be mediated through inherent differences in regional mitochondrial function. To investigate regional cerebral mitochondrial energetics, the rates of Oxygen Consumption and adenosine-5'-triphosphate (ATP) synthesis were assessed in isolated non-synaptic mitochondria of the cerebral cortex, hippocampus, and striatum of the male mouse Brain. Oxygen Consumption rates were assessed using a Seahorse XFe96 analyzer and ATP synthesis rates were determined by an online luciferin-luciferase coupled luminescence assay. Complex I- and complex II-driven respiration and ATP synthesis, were investigated by applying pyruvate in combination with malate, or succinate, as respiratory substrates, respectively. Hippocampal mitochondria exhibited the lowest basal and adenosine-5'-diphosphate (ADP)-stimulated rate of Oxygen Consumption when provided pyruvate and malate. However, hippocampal mitochondria also exhibited an increased proton leak and an elevated relative rate of Oxygen Consumption in response to the uncoupler carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP), showing a large capacity for uncoupled respiration in the presence of pyruvate. When the complex II-linked substrate succinate was provided, striatal mitochondria exhibited the highest respiration and ATP synthesis rate, whereas hippocampal mitochondria had the lowest. However, the mitochondrial efficiency, determined as ATP produced/O2 consumed, was similar between the three regions. This study reveals inherent differences in regional mitochondrial energetics and may serve as a tool for further investigations of regional mitochondrial function in relation to neurodegenerative diseases.
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Distinct differences in rates of Oxygen Consumption and ATP synthesis of regionally isolated non‐synaptic mouse Brain mitochondria
Journal of Neuroscience Research, 2019Co-Authors: Jens V Andersen, Emil Jakobsen, Helle S Waagepetersen, Blanca I AldanaAbstract:: Brain mitochondrial dysfunction has been implicated in several neurodegenerative diseases. The distribution and efficiency of mitochondria display large heterogeneity throughout the regions of the Brain. This may imply that the selective regional susceptibility of neurodegenerative diseases could be mediated through inherent differences in regional mitochondrial function. To investigate regional cerebral mitochondrial energetics, the rates of Oxygen Consumption and adenosine-5'-triphosphate (ATP) synthesis were assessed in isolated non-synaptic mitochondria of the cerebral cortex, hippocampus, and striatum of the male mouse Brain. Oxygen Consumption rates were assessed using a Seahorse XFe96 analyzer and ATP synthesis rates were determined by an online luciferin-luciferase coupled luminescence assay. Complex I- and complex II-driven respiration and ATP synthesis, were investigated by applying pyruvate in combination with malate, or succinate, as respiratory substrates, respectively. Hippocampal mitochondria exhibited the lowest basal and adenosine-5'-diphosphate (ADP)-stimulated rate of Oxygen Consumption when provided pyruvate and malate. However, hippocampal mitochondria also exhibited an increased proton leak and an elevated relative rate of Oxygen Consumption in response to the uncoupler carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP), showing a large capacity for uncoupled respiration in the presence of pyruvate. When the complex II-linked substrate succinate was provided, striatal mitochondria exhibited the highest respiration and ATP synthesis rate, whereas hippocampal mitochondria had the lowest. However, the mitochondrial efficiency, determined as ATP produced/O2 consumed, was similar between the three regions. This study reveals inherent differences in regional mitochondrial energetics and may serve as a tool for further investigations of regional mitochondrial function in relation to neurodegenerative diseases.
Douglas L Rothman - One of the best experts on this subject based on the ideXlab platform.
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Simultaneous Determination of the Rates of the TCA Cycle, Glucose Utilization, α-Ketoglutarate/Glutamate Exchange, and Glutamine Synthesis in Human Brain by NMR
Journal of Cerebral Blood Flow and Metabolism, 2016Co-Authors: Graeme F Mason, Kevin L Behar, Douglas L Rothman, Rolf Gruetter, Robert G Shulman, Edward J NovotnyAbstract:13C isotopic tracer data previously obtained by 13C nuclear magnetic resonance in the human Brain in vivo were analyzed using a mathematical model to determine metabolic rates in a region of the human neocortex. The tricarboxylic acid (TCA) cycle rate was 0.73 ± 0.19 μmol min-1 g-1 (mean ± SD; n = 4). The standard deviation reflects primarily intersubject variation, since individual uncertainties were low. The rate of α- ketoglutarate/glutamate exchange was 57 ± 26 μmol min-1 g-1 (n = 3), which is much greater than the TCA cycle rate; the high rate indicates that α-ketoglutarate and glutamate are in rapid exchange and can be treated as a single combined kinetic pool. The rate of synthesis of glutamine from glutamate was 0.47 μmol min-1 g-1 (n = 4), with 95% confidence limits of 0.139 and 3.094 μmol min-1 g-1; individual uncertainties were biased heavily toward high synthesis rates. From the TCA cycle rate the Brain Oxygen Consumption was estimated to be 2.14 ± 0.48 μmol min-1 g-1 (5.07 ± 1.14 ml 100 g-1 min-1; n = 4), and the rate of Brain glucose Consumption was calculated to be 0.37 ± 0.08 μmol min-1 g-1 (n = 4). The sensitivity of the model to the assumptions made was evaluated, and the calculated values were found to be unchanged as long as the assumptions remained near reported physiological values.
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astroglial contribution to Brain energy metabolism in humans revealed by 13c nuclear magnetic resonance spectroscopy elucidation of the dominant pathway for neurotransmitter glutamate repletion and measurement of astrocytic oxidative metabolism
The Journal of Neuroscience, 2002Co-Authors: Vincent Lebon, Kitt Falk Petersen, Gary W Cline, Jun Shen, Graeme F Mason, Sylvie Dufour, Kevin L Behar, Gerald I Shulman, Douglas L RothmanAbstract:Increasing evidence supports a crucial role for glial metabolism in maintaining proper synaptic function and in the etiology of neurological disease. However, the study of glial metabolism in humans has been hampered by the lack of noninvasive methods. To specifically measure the contribution of astroglia to Brain energy metabolism in humans, we used a novel noninvasive nuclear magnetic resonance spectroscopic approach. We measured carbon 13 incorporation into Brain glutamate and glutamine in eight volunteers during an intravenous infusion of [2-13C] acetate, which has been shown in animal models to be metabolized specifically in astroglia. Mathematical modeling of the three established pathways for neurotransmitter glutamate repletion indicates that the glutamate/glutamine neurotransmitter cycle between astroglia and neurons (0.32 ± 0.07 μmol · gm−1 · min−1) is the major pathway for neuronal glutamate repletion and that the astroglial TCA cycle flux (0.14 ± 0.06 μmol · gm−1 · min−1) accounts for ∼14% of Brain Oxygen Consumption. Up to 30% of the glutamine transferred to the neurons by the cycle may derive from replacement of oxidized glutamate by anaplerosis. The further application of this approach could potentially enlighten the role of astroglia in supporting Brain glutamatergic activity and in neurological and psychiatric disease.
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simultaneous determination of the rates of the tca cycle glucose utilization α ketoglutarate glutamate exchange and glutamine synthesis in human Brain by nmr
Journal of Cerebral Blood Flow and Metabolism, 1995Co-Authors: Graeme F Mason, Kevin L Behar, Douglas L Rothman, Rolf Gruetter, Robert G Shulman, Edward J NovotnyAbstract:13C isotopic tracer data previously obtained by 13C nuclear magnetic resonance in the human Brain in vivo were analyzed using a mathematical model to determine metabolic rates in a region of the human neocortex. The tricarboxylic acid (TCA) cycle rate was 0.73 ± 0.19 μmol min-1 g-1 (mean ± SD; n = 4). The standard deviation reflects primarily intersubject variation, since individual uncertainties were low. The rate of α- ketoglutarate/glutamate exchange was 57 ± 26 μmol min-1 g-1 (n = 3), which is much greater than the TCA cycle rate; the high rate indicates that α-ketoglutarate and glutamate are in rapid exchange and can be treated as a single combined kinetic pool. The rate of synthesis of glutamine from glutamate was 0.47 μmol min-1 g-1 (n = 4), with 95% confidence limits of 0.139 and 3.094 μmol min-1 g-1; individual uncertainties were biased heavily toward high synthesis rates. From the TCA cycle rate the Brain Oxygen Consumption was estimated to be 2.14 ± 0.48 μmol min-1 g-1 (5.07 ± 1.14 ml 100 g-1 min-1; n = 4), and the rate of Brain glucose Consumption was calculated to be 0.37 ± 0.08 μmol min-1 g-1 (n = 4). The sensitivity of the model to the assumptions made was evaluated, and the calculated values were found to be unchanged as long as the assumptions remained near reported physiological values.
Graeme F Mason - One of the best experts on this subject based on the ideXlab platform.
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Simultaneous Determination of the Rates of the TCA Cycle, Glucose Utilization, α-Ketoglutarate/Glutamate Exchange, and Glutamine Synthesis in Human Brain by NMR
Journal of Cerebral Blood Flow and Metabolism, 2016Co-Authors: Graeme F Mason, Kevin L Behar, Douglas L Rothman, Rolf Gruetter, Robert G Shulman, Edward J NovotnyAbstract:13C isotopic tracer data previously obtained by 13C nuclear magnetic resonance in the human Brain in vivo were analyzed using a mathematical model to determine metabolic rates in a region of the human neocortex. The tricarboxylic acid (TCA) cycle rate was 0.73 ± 0.19 μmol min-1 g-1 (mean ± SD; n = 4). The standard deviation reflects primarily intersubject variation, since individual uncertainties were low. The rate of α- ketoglutarate/glutamate exchange was 57 ± 26 μmol min-1 g-1 (n = 3), which is much greater than the TCA cycle rate; the high rate indicates that α-ketoglutarate and glutamate are in rapid exchange and can be treated as a single combined kinetic pool. The rate of synthesis of glutamine from glutamate was 0.47 μmol min-1 g-1 (n = 4), with 95% confidence limits of 0.139 and 3.094 μmol min-1 g-1; individual uncertainties were biased heavily toward high synthesis rates. From the TCA cycle rate the Brain Oxygen Consumption was estimated to be 2.14 ± 0.48 μmol min-1 g-1 (5.07 ± 1.14 ml 100 g-1 min-1; n = 4), and the rate of Brain glucose Consumption was calculated to be 0.37 ± 0.08 μmol min-1 g-1 (n = 4). The sensitivity of the model to the assumptions made was evaluated, and the calculated values were found to be unchanged as long as the assumptions remained near reported physiological values.
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astroglial contribution to Brain energy metabolism in humans revealed by 13c nuclear magnetic resonance spectroscopy elucidation of the dominant pathway for neurotransmitter glutamate repletion and measurement of astrocytic oxidative metabolism
The Journal of Neuroscience, 2002Co-Authors: Vincent Lebon, Kitt Falk Petersen, Gary W Cline, Jun Shen, Graeme F Mason, Sylvie Dufour, Kevin L Behar, Gerald I Shulman, Douglas L RothmanAbstract:Increasing evidence supports a crucial role for glial metabolism in maintaining proper synaptic function and in the etiology of neurological disease. However, the study of glial metabolism in humans has been hampered by the lack of noninvasive methods. To specifically measure the contribution of astroglia to Brain energy metabolism in humans, we used a novel noninvasive nuclear magnetic resonance spectroscopic approach. We measured carbon 13 incorporation into Brain glutamate and glutamine in eight volunteers during an intravenous infusion of [2-13C] acetate, which has been shown in animal models to be metabolized specifically in astroglia. Mathematical modeling of the three established pathways for neurotransmitter glutamate repletion indicates that the glutamate/glutamine neurotransmitter cycle between astroglia and neurons (0.32 ± 0.07 μmol · gm−1 · min−1) is the major pathway for neuronal glutamate repletion and that the astroglial TCA cycle flux (0.14 ± 0.06 μmol · gm−1 · min−1) accounts for ∼14% of Brain Oxygen Consumption. Up to 30% of the glutamine transferred to the neurons by the cycle may derive from replacement of oxidized glutamate by anaplerosis. The further application of this approach could potentially enlighten the role of astroglia in supporting Brain glutamatergic activity and in neurological and psychiatric disease.
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simultaneous determination of the rates of the tca cycle glucose utilization α ketoglutarate glutamate exchange and glutamine synthesis in human Brain by nmr
Journal of Cerebral Blood Flow and Metabolism, 1995Co-Authors: Graeme F Mason, Kevin L Behar, Douglas L Rothman, Rolf Gruetter, Robert G Shulman, Edward J NovotnyAbstract:13C isotopic tracer data previously obtained by 13C nuclear magnetic resonance in the human Brain in vivo were analyzed using a mathematical model to determine metabolic rates in a region of the human neocortex. The tricarboxylic acid (TCA) cycle rate was 0.73 ± 0.19 μmol min-1 g-1 (mean ± SD; n = 4). The standard deviation reflects primarily intersubject variation, since individual uncertainties were low. The rate of α- ketoglutarate/glutamate exchange was 57 ± 26 μmol min-1 g-1 (n = 3), which is much greater than the TCA cycle rate; the high rate indicates that α-ketoglutarate and glutamate are in rapid exchange and can be treated as a single combined kinetic pool. The rate of synthesis of glutamine from glutamate was 0.47 μmol min-1 g-1 (n = 4), with 95% confidence limits of 0.139 and 3.094 μmol min-1 g-1; individual uncertainties were biased heavily toward high synthesis rates. From the TCA cycle rate the Brain Oxygen Consumption was estimated to be 2.14 ± 0.48 μmol min-1 g-1 (5.07 ± 1.14 ml 100 g-1 min-1; n = 4), and the rate of Brain glucose Consumption was calculated to be 0.37 ± 0.08 μmol min-1 g-1 (n = 4). The sensitivity of the model to the assumptions made was evaluated, and the calculated values were found to be unchanged as long as the assumptions remained near reported physiological values.
Edward J Novotny - One of the best experts on this subject based on the ideXlab platform.
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Simultaneous Determination of the Rates of the TCA Cycle, Glucose Utilization, α-Ketoglutarate/Glutamate Exchange, and Glutamine Synthesis in Human Brain by NMR
Journal of Cerebral Blood Flow and Metabolism, 2016Co-Authors: Graeme F Mason, Kevin L Behar, Douglas L Rothman, Rolf Gruetter, Robert G Shulman, Edward J NovotnyAbstract:13C isotopic tracer data previously obtained by 13C nuclear magnetic resonance in the human Brain in vivo were analyzed using a mathematical model to determine metabolic rates in a region of the human neocortex. The tricarboxylic acid (TCA) cycle rate was 0.73 ± 0.19 μmol min-1 g-1 (mean ± SD; n = 4). The standard deviation reflects primarily intersubject variation, since individual uncertainties were low. The rate of α- ketoglutarate/glutamate exchange was 57 ± 26 μmol min-1 g-1 (n = 3), which is much greater than the TCA cycle rate; the high rate indicates that α-ketoglutarate and glutamate are in rapid exchange and can be treated as a single combined kinetic pool. The rate of synthesis of glutamine from glutamate was 0.47 μmol min-1 g-1 (n = 4), with 95% confidence limits of 0.139 and 3.094 μmol min-1 g-1; individual uncertainties were biased heavily toward high synthesis rates. From the TCA cycle rate the Brain Oxygen Consumption was estimated to be 2.14 ± 0.48 μmol min-1 g-1 (5.07 ± 1.14 ml 100 g-1 min-1; n = 4), and the rate of Brain glucose Consumption was calculated to be 0.37 ± 0.08 μmol min-1 g-1 (n = 4). The sensitivity of the model to the assumptions made was evaluated, and the calculated values were found to be unchanged as long as the assumptions remained near reported physiological values.
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simultaneous determination of the rates of the tca cycle glucose utilization α ketoglutarate glutamate exchange and glutamine synthesis in human Brain by nmr
Journal of Cerebral Blood Flow and Metabolism, 1995Co-Authors: Graeme F Mason, Kevin L Behar, Douglas L Rothman, Rolf Gruetter, Robert G Shulman, Edward J NovotnyAbstract:13C isotopic tracer data previously obtained by 13C nuclear magnetic resonance in the human Brain in vivo were analyzed using a mathematical model to determine metabolic rates in a region of the human neocortex. The tricarboxylic acid (TCA) cycle rate was 0.73 ± 0.19 μmol min-1 g-1 (mean ± SD; n = 4). The standard deviation reflects primarily intersubject variation, since individual uncertainties were low. The rate of α- ketoglutarate/glutamate exchange was 57 ± 26 μmol min-1 g-1 (n = 3), which is much greater than the TCA cycle rate; the high rate indicates that α-ketoglutarate and glutamate are in rapid exchange and can be treated as a single combined kinetic pool. The rate of synthesis of glutamine from glutamate was 0.47 μmol min-1 g-1 (n = 4), with 95% confidence limits of 0.139 and 3.094 μmol min-1 g-1; individual uncertainties were biased heavily toward high synthesis rates. From the TCA cycle rate the Brain Oxygen Consumption was estimated to be 2.14 ± 0.48 μmol min-1 g-1 (5.07 ± 1.14 ml 100 g-1 min-1; n = 4), and the rate of Brain glucose Consumption was calculated to be 0.37 ± 0.08 μmol min-1 g-1 (n = 4). The sensitivity of the model to the assumptions made was evaluated, and the calculated values were found to be unchanged as long as the assumptions remained near reported physiological values.
Jens V Andersen - One of the best experts on this subject based on the ideXlab platform.
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distinct differences in rates of Oxygen Consumption and atp synthesis of regionally isolated non synaptic mouse Brain mitochondria
Journal of Neuroscience Research, 2019Co-Authors: Jens V Andersen, Emil Jakobsen, Helle S Waagepetersen, Blanca I AldanaAbstract:Brain mitochondrial dysfunction has been implicated in several neurodegenerative diseases. The distribution and efficiency of mitochondria display large heterogeneity throughout the regions of the Brain. This may imply that the selective regional susceptibility of neurodegenerative diseases could be mediated through inherent differences in regional mitochondrial function. To investigate regional cerebral mitochondrial energetics, the rates of Oxygen Consumption and adenosine-5'-triphosphate (ATP) synthesis were assessed in isolated non-synaptic mitochondria of the cerebral cortex, hippocampus, and striatum of the male mouse Brain. Oxygen Consumption rates were assessed using a Seahorse XFe96 analyzer and ATP synthesis rates were determined by an online luciferin-luciferase coupled luminescence assay. Complex I- and complex II-driven respiration and ATP synthesis, were investigated by applying pyruvate in combination with malate, or succinate, as respiratory substrates, respectively. Hippocampal mitochondria exhibited the lowest basal and adenosine-5'-diphosphate (ADP)-stimulated rate of Oxygen Consumption when provided pyruvate and malate. However, hippocampal mitochondria also exhibited an increased proton leak and an elevated relative rate of Oxygen Consumption in response to the uncoupler carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP), showing a large capacity for uncoupled respiration in the presence of pyruvate. When the complex II-linked substrate succinate was provided, striatal mitochondria exhibited the highest respiration and ATP synthesis rate, whereas hippocampal mitochondria had the lowest. However, the mitochondrial efficiency, determined as ATP produced/O2 consumed, was similar between the three regions. This study reveals inherent differences in regional mitochondrial energetics and may serve as a tool for further investigations of regional mitochondrial function in relation to neurodegenerative diseases.
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Distinct differences in rates of Oxygen Consumption and ATP synthesis of regionally isolated non‐synaptic mouse Brain mitochondria
Journal of Neuroscience Research, 2019Co-Authors: Jens V Andersen, Emil Jakobsen, Helle S Waagepetersen, Blanca I AldanaAbstract:: Brain mitochondrial dysfunction has been implicated in several neurodegenerative diseases. The distribution and efficiency of mitochondria display large heterogeneity throughout the regions of the Brain. This may imply that the selective regional susceptibility of neurodegenerative diseases could be mediated through inherent differences in regional mitochondrial function. To investigate regional cerebral mitochondrial energetics, the rates of Oxygen Consumption and adenosine-5'-triphosphate (ATP) synthesis were assessed in isolated non-synaptic mitochondria of the cerebral cortex, hippocampus, and striatum of the male mouse Brain. Oxygen Consumption rates were assessed using a Seahorse XFe96 analyzer and ATP synthesis rates were determined by an online luciferin-luciferase coupled luminescence assay. Complex I- and complex II-driven respiration and ATP synthesis, were investigated by applying pyruvate in combination with malate, or succinate, as respiratory substrates, respectively. Hippocampal mitochondria exhibited the lowest basal and adenosine-5'-diphosphate (ADP)-stimulated rate of Oxygen Consumption when provided pyruvate and malate. However, hippocampal mitochondria also exhibited an increased proton leak and an elevated relative rate of Oxygen Consumption in response to the uncoupler carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP), showing a large capacity for uncoupled respiration in the presence of pyruvate. When the complex II-linked substrate succinate was provided, striatal mitochondria exhibited the highest respiration and ATP synthesis rate, whereas hippocampal mitochondria had the lowest. However, the mitochondrial efficiency, determined as ATP produced/O2 consumed, was similar between the three regions. This study reveals inherent differences in regional mitochondrial energetics and may serve as a tool for further investigations of regional mitochondrial function in relation to neurodegenerative diseases.
